Semiconducting nanowires have the potential to function as highly sensitive and selective sensors for the label-free detection of low concentrations of pathogenic microorganisms. Successful solution-phase nanowire sensing has been demonstrated for ions, small molecules, proteins, DNA and viruses; however, 'bottom-up' nanowires (or similarly configured carbon nanotubes) used for these demonstrations require hybrid fabrication schemes, which result in severe integration issues that have hindered widespread application. Alternative 'top-down' fabrication methods of nanowire-like devices produce disappointing performance because of process-induced material and device degradation. Here we report an approach that uses complementary metal oxide semiconductor (CMOS) field effect transistor compatible technology and hence demonstrate the specific label-free detection of below 100 femtomolar concentrations of antibodies as well as real-time monitoring of the cellular immune response. This approach eliminates the need for hybrid methods and enables system-scale integration of these sensors with signal processing and information systems. Additionally, the ability to monitor antibody binding and sense the cellular immune response in real time with readily available technology should facilitate widespread diagnostic applications.

Recent developments in the application of micro- and nanosystems for drug administration include a diverse range of new materials and methods. New approaches include the on-demand activation of molecular interactions, novel diffusion-controlled delivery devices, nanostructured 'smart' surfaces and materials, and prospects for coupling drug delivery to sensors and implants. Micro- and nanotechnologies are enabling the design of novel methods such as radio-frequency addressing of individual molecules or the suppression of immune response to a release device. Current challenges include the need to balance the small scale of the devices with the quantities of drugs that are clinically necessary, the requirement for more stable sensor platforms, and the development of methods to evaluate these new materials and devices for safety and efficacy.

Since the discovery of surfactant-templated silica mesophasesl, the development of organic modification schemes to impart functionality to the pore surfaces has received much attention2-13. Most recently, using the general class of compounds referred to as Here we use an evaporation-induced self-assembly procedure20 to prepare BSQM films and spherical nanoparticles. Capacitance-voltage measurements along with a variety of 1

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Nucleic acid ligands (aptamers) are potentially well suited for the therapeutic targeting of drug encapsulated controlled release polymer particles in a cell-or tissue-specific manner. We synthesized a bioconjugate composed of controlled release polymer nanoparticles and aptamers and examined its efficacy for targeted delivery to prostate cancer cells. Specifically, we synthesized poly(lactic acid)-block-polyethylene glycol (PEG) copolymer with a terminal carboxylic acid functional group (PLA-PEG-COOH), and encapsulated rhodamine-labeled dextran (as a model drug) within PLA-PEG-COOH nanoparticles. These nanoparticles have the following desirable characteristics: (a) negative surface charge (؊50 ؎ 3 mV, mean ؎ SD, n ‫؍‬ 3), which may minimize nonspecific interaction with the negatively charged nucleic acid aptamers; (b) carboxylic acid groups on the particle surface for potential modification and covalent conjugation to amine-modified aptamers; and (c) presence of PEG on particle surface, which enhances circulating half-life while contributing to decreased uptake in nontargeted cells. Next, we generated nanoparticle-aptamer bioconjugates with RNA aptamers that bind to the prostate-specific membrane antigen, a well-known prostate cancer tumor marker that is overexpressed on prostate acinar epithelial cells. We demonstrated that these bioconjugates can efficiently target and get taken up by the prostate LNCaP epithelial cells, which express the prostate-specific membrane antigen protein (77-fold increase in binding versus control, n ‫؍‬ 150 cells per group). In contrast to LNCaP cells, the uptake of these particles is not enhanced in cells that do not express the prostate-specific membrane antigen protein. To our knowledge, this represents the first report of targeted drug delivery with nanoparticle-aptamer bioconjugates.

A platform for controlled drug delivery using a conductive‐polymer substrate has been created. Through the incorporation of biotin into the conductive polymer polypyrrole (PPy) and the subsequent attachment of the desired drug molecule (such as nerve growth factor, NGF) via a streptavidin linker, an applied potential can trigger release of the drug from the polymer surface (see figure).

Advances in new micro- and nanotechnologies are accelerating the identification and evaluation of drug candidates, and the development of new delivery technologies that are required to transform biological potential into medical reality. This article will highlight the emerging micro- and nanotechnology tools, techniques and devices that are being applied to advance the fields of drug discovery and drug delivery. Many of the promising applications of micro- and nanotechnology are likely to occur at the interfaces between microtechnology, nanotechnology and biochemistry.

Cell membranes contain numerous nanoscale conductors in the form of ion channels and ion pumps [1][2][3][4] that work together to form ion concentration gradients across the membrane, which can be triggered to release an action potential (AP) 1,5 . We ask if artificial cells can be built to utilize ion transport as effectively as natural cells. Here we used the electrogenic cell (electrocyte) of an electric eel to model the formation of AP by tracking the conversion of ion concentration gradients into APs across the different nanoscale conductors. Using the parameters extracted from the model, we designed an artificial cell based on an optimized selection of conductors. The resulting cell is similar to the electrocyte but has higher power output density and greater energy conversion efficiency. We suggest methods for producing these artificial cells that have applications in powering medical implants and other tiny devices.The electrocyte in an electric eel (Electrophorus electricus) can generate potentials of about 600V 2,3,6 to stun prey and ward off predators (Fig. 1a). The transmembrane proteins in the electrocytes are asymmetrically distributed across two primary membranes, one innervated and the other non-innervated (Fig. 1b), and are separated by an insulating septa (wall). The non-innervated membrane has numerous sodium potassium ATPase pumps (Na + /K + ) and both K + and chloride (Cl − ) channels. The innervated membrane contains high densities of acetylcholine receptors (AChRs), voltage-gated Na+ channels (which are responsible for activating APs), voltage-gated K + channels (Kvs) 7 , inward rectifier K + channels (Kirs, which are ion channels that stop ion flow when the membrane is depolarized) 6 and leak channels.When the chemical agonist, acetylcholine (ACh), is released into the junction between the AChR and another nearby excitable cell (synapse), AChRs bind with ACh and become permeable to the cations, Na + and K + . This opens the AChRs and depolarizes the innervated membrane, raising the probability that voltage-gated Na + channels will open (Fig. 1c) 3,6,8 . Depolarization causes the normally negative innervated cell membrane potential to become positive with respect to the potential on the non-innervated membrane. With Na + flowing into the cell, the innervated membrane potential further increases, causing the opening of additional voltage-gated Na + channels. This cascade of AChRs opening large number of Na + channels results in AP formation on the innervated membrane. The Kir channels are closed during this stage, which speeds the increase of the membrane potential. The maximum innervated 5,6 . The non-innervated membrane potential remains at approximately −85mV due to ATPase, K + channel and Cl − activity 2,5,6 . After the peak of the AP, the innervated membrane is repolarized with the inactivation of Na + channels 8 and the opening of Kir and Kvs channels. Ion flux through leak channels further expedites the restoration of membrane potential to the resting state (−85mV). The ion ...